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Homogeneously Staining Region in Anthracycline-resistant HL-60/AR Cells not Associated with MDR1 Amplification¹

Winthrop University Hospital, Division of Oncology/Hematology, Mineola, New York 11501 [A. A. H., M. S., S. G., D. C., J. D.]; Cancer Research Laboratories, Queen's University, Kingston, Ontario, Canada K7L 3N6 [E. R. C., J. H. G., M. J. P., S. P., S. P. C. C.]; Division of Medical Oncology, Department of Medicine, Columbia College of Physicians and Surgeons, New York, New York 10032 [J. E. G., R. N. T., S. K., M. R.]; Department of Genetics and Development, Columbia University, New York, New York 10032 [D. W., M. T. Y.]; and Toronto General Hospital, Toronto, Ontario, Canada M5G 1L7 [M. A. B.]; Division of Medical Oncology, University of California, Irvine, California 92717 [J. L.]

Anthracycline-resistant HL-60/AR cells and their drug-sensitive HL-60/S counterparts were characterized by karyotypic analysis and examined for the overexpression of DNA and mRNA sequences coding for P-glycoprotein (Pgp). The HL-60/S cells were karyotypically stable over a 5-year period of study (1986–1991), except for an additional small Giemsa-positive band noted at 7q22 in cultures harvested in 1987, but not in 1986. This change did not affect drug sensitivity. The drug-resistant HL-60/AR cells examined in 1986, 1987, and 1991 demonstrated a very stable karyotype. The most striking feature was a large homogeneously staining region in the long arm of chromosome 7 (7q11.2), and translocation of the remainder of the long arm to another centromere. Other changes in the HL-60/AR cells included inversion in 9q, partial deletion of the short arm of chromosome 10p, addition of material to the p arm of der(16), loss of chromosome 22, and the appearance of a new marker chromosome.

Both HL-60/S and the HL-60/AR cells were found not to amplify DNA or mRNA sequences coding for the Pgp. Thus, although the HL-60/AR cells possess the classical multidrug resistance phenotype and demonstrate a homogeneously staining region near the region of the MDR1 gene, their resistance is due to mechanisms other than those coded for by MDR1.

¹ Supported by the National Cancer Institute of Canada, Grants 2215 (J. H. G.) and 2049 (S. P. C. C.); ACS CH-357 (A. A. H.); Clare Nelson Bequest of Kingston General Hospital (J. H. G.); the National Cancer Institute, CA-42450; the William J. Matheson Foundation; the Medical Research Council of Canada; and the National Cancer Institute of Canada.

² To whom requests for reprints should be addressed, at Winthrop University Hospital, Division of Oncology/Hematology, Professional Building, 222 Station Plaza N., Suite 300, Mineola, NY 11501.

Received 3/ 6/92. Accepted 7/21/92.